During the past decade, the relationship between monoamine uptake and a variety of diseases and conditions has been appreciated and investigated. For example, the hydrochloride salt of fluoxetine ((dl-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamine)) is a selective serotonin (5-hydroxytryptamine) uptake inhibitor which has been approved by the Food and Drug Administration (FDA) for the treatment of depression and is also presently undergoing clinical evaluation for the treatment of eating disorders, alcoholism, and other disorders. Similarly, tomoxetine hydrochloride (-)-N-methyl-3-phenyl-3-(2-methyl-phenoxy)hydrochloride) is a selective inhibitor of norepinephrine uptake that is being investigated clinically for its antidepressant activity.
These compounds are among many taught in U.S. Pat. Nos. 4,018,895, 4,194,009, and 4,314,081 as being potent blockers of the uptake of various physiologically active monoamines including serotonin, norepinephrine and dopamine. U.S. Pat. No. 4,207,343 discloses 1-phenyl-3(substituted phenoxy)propanamines as having the ability to block the uptake of a variety of monoamines.
More recently, U.S. Pat. No. 5,135,947 discloses 1-phenyl-3-naphthalenyloxypropanamines and their use as selective serotonin receptive inhibitors. The previously available synthetic route to 1-phenyl-3-naphthalenyloxypropanamines, however, requires a chemical resolution to arrive at the chiral center. This invention provides intermediates to 1-phenyl-3-naphthalenyloxypropanamines that can be prepared in a high state of optical purity with little or no racemization. A further advantage is that these intermediates are derived from cheap and readily available products.